MicroRNAs: emerging players in apical periodontitis

Abstract

Apical periodontitis is an inflammatory disorder of periradicular tissues developed from endodontic infections. Understanding its pathophysiology and the underlying molecular mechanisms is key to the advancement of endodontics. MicroRNAs (miRNAs), a group of evolutionarily conserved small non-coding RNAs, may be phenotypically and functionally associated with the pathogenesis of apical periodontitis. Several studies have focused on the role of miRNAs in the pulp and periradicular biology, and they have demonstrated their essential functions, such as initiating odontogenic differentiation and promoting pro- or anti-inflammatory responses in pulpitis. Up to date, over 2,000 miRNAs have been discovered in humans; however, only few have been reported to associate with apical periodontitis. Therefore, identifying miRNAs involved in diseased apical tissues and conducting functional studies are important in expanding our current knowledge of pulp and periradicular biology and exploring novel therapeutic avenues. In this review, we revisit current models of apical periodontitis and miRNA biogenesis, analyze existing evidence of the involvement of miRNAs in diseased apical tissues, and discuss their diverse functions and potential values. Based on their sheer abundance, prolonged stability in biofluid, and relative ease of sampling, miRNAs may be a useful tool to be developed as diagnostic biomarkers for apical periodontitis. Furthermore, it can be used as therapeutic targets in conjunction with conventional endodontic therapies.

MiR-199a-5P promotes osteogenic differentiation of human stem cells from apical papilla via targeting IFIT2 in apical periodontitis

“…Most importantly, miRNAs have been implicated as valid regulators that can modulate multiple biological processes, including bone regeneration and anti-inflammatory response (46, 47). As Shen and Silva (25) have reported that over 100 miRNAs were differentially expressed in AP and the highest expression of miR-10a-5p appeared to be involved in triggering anti-inflammatory signaling and promoting healing. It is noteworthy that different phases of inflammatory conditions may have different effects on the bone regenerative capacity of stem cells, as (48) showed that long-term exposure to pro-inflammatory cytokines inhibited the osteogenic differentiation of SCAPs.…”

“…Inflammation of periapical tissues commonly presents with the destruction of the alveolar bone, which is generally treated by controlling the infection and eliminating the inflammation to promote the repair of the periapical bone defects ( 40 – 43 ). Currently, miRNAs, transglutaminases, and other agents have been found to be involved in the development and progression of oral diseases ( 25 , 44 , 45 ). Most importantly, miRNAs have been implicated as valid regulators that can modulate multiple biological processes, including bone regeneration and anti-inflammatory response ( 46 , 47 ).…”

“…The pivotal roles of miRNAs in osteogenesis, such as osteoblast differentiation, angiogenesis, and intra-chondral bone formation have also been identified (21)(22)(23). Additionally, previous studies have revealed that miRNAs may play crucial roles in the development and progression of oral diseases, such as apical periodontitis, pulpitis and periodontitis (24)(25)(26)(27). However, among more than 2,000 miRNAs identified in humans, only a few were reportedly involved in apical periodontitis (28-30) although their role in regulating osteogenesis of hSCAPs and in clinical apical periodontitis samples have not been validated.…”

Plasma Rich in Growth Factors in the Treatment of Endodontic Periapical Lesions in Adult Patients: A Narrative Review

“…Table 2 presents the exemplary miRNA occurring within the periapical lesions on the basis of the literature [61,[68][69][70][71][72].…”

Double-Edged Sword Effect of Pyroptosis: The Role of Caspase-1/-4/-5/-11 in Different Levels of Apical Periodontitis

“…), cytokines, chemokines, RANK/RANKL/OPG system and neuropeptides [ 2 , 7 ], which influence the balance between tissue destruction and regeneration in AP [ 7 ]. Innumerable investigations have been conducted to study the pathogenesis of AP and this dynamic shift; however, the exact etiological factors and the mechanisms associated with molecular changes has been not well elucidated [ 8 , 9 ]. What is the crucial factor in mediating this homeostasis in a periapical lesion?…”